JAX
Mouse Strain Datasheet - 007848
BXSB.129P2(Cg)-Tcratm1Mjo/TheoJ
BXSB-Tcrα-/- homozygotes lack αβ+ T cells and do not develop the spontaneous lupus symptoms normally associated with the BXSB recombinant inbred genetic background. These BXSB-Tcrα-/- mice may be useful for adoptive transfer experiments for studying the role of T cells in systemic autoimmunity and lupus.
Donating Investigator
Argyrios N Theofilopoulos, The Scripps Research Institute
Genetic overview
| Genetic Background | Generation |
|---|---|
|
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Tcratm1Mjo
| Allele Type | Gene Symbol | Gene Name |
|---|---|---|
| Targeted (Null/Knockout) | Tcra | T cell receptor alpha chain |
Research Applications
- Cancer Research
- Cell Biology Research
- Immunology, Inflammation and Autoimmunity Research
- Research Tools
- Hematological Research
Detailed Description
Male mice on the BXSB recombinant inbred genetic background (see Stock No. 000740) develop spontaneous autoimmune disease closely resembling the human disease systemic lupus erythematosus (SLE), including moderate lymph node and spleen enlargement, hemolytic anemia, hypergammaglobulinemia, and immune complex glomerulonephritis. This autoimmune phenotype is associated with at least six non-MHC loci (the Y chromosome linked Yaa, Bxs1-4 on chromosome 1 and Bxs6 on chromosome 13) and defined by increased homeostatic proliferation of self-reactive T cells. Because these BXSB-Tcrα-/- mice are homozygous for the Tcrα targeted mutation, they lack αβ+ T cells and do not develop spontaneous lupus symptoms. These BXSB-Tcrα-/- mice may be useful for adoptive transfer experiments for studying the role of T cells in systemic autoimmunity and lupus.
Development
A targeting vector (isolated from a genomic library of embryonic BALB/c DNA) was designed to disrupt the Tcrα-C element C1 constant region of the gene with a neomycin cassette. This construct was electroporated into 129P2/OlaHsd-derived GK129 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts and chimeric founders were bred to BALB/c to generate mutant mice. These mice were then crossed with C57BL/6 inbred mice in the laboratory of Dr. Michael J. Owen (Imperial Cancer Research Fund). Mice were then sent to Dr. Argyrios N. Theofilopoulos (The Scripps Research Institute) and subsequently backcrossed to their stocks of the BXSB recombinant inbred strain (BXSB/MpScr) for at least 6 generations prior to arrival at The Jackson Laboratory. Upon arrival, mutant mice were bred with the BXSB/MpJ recombinant inbred strain (Stock No. 000740) for at least one generation to establish the mutant colony.
Control Suggestions
Selected References
- Lawson BR; Koundouris SI; Barnhouse M; Dummer W; Baccala R; Kono DH; Theofilopoulos AN. 2001. The role of alpha beta+ T cells and homeostatic T cell proliferation in Y-chromosome-associated murine lupus. J Immunol 167(4):2354-60. PubMed: 11490025MGI: J:120153
Tcratm1Mjo
Allele Symbol: Tcratm1Mjo
| Allele Name | targeted mutation 1, Michael J Owen |
|---|---|
| Allele Type | Targeted (Null/Knockout) |
| Allele Synonym(s) | Calpha-; TCRalpha; TCRalpha KO; TCRalphae-; Tcratm1Phi; Tcralpha- |
| Gene Symbol and Name | Tcra, T cell receptor alpha chain |
| Gene Synonym(s) | Tcr alpha; Tcralpha |
| Strain of Origin | 129P2/OlaHsd |
| Chromosome | 14 |
| Molecular Note | The Tcra-C element C1 was disrupted by the insertion of a neomycin selection cassette. |
| Mutations Made By | Michael Owen, Imperial Cancer Research Fund |
Disease Terms
Research Areas By Genotype
This mouse can be used to support research in many areas including:
- Cancer Research
- Toxicology
- xenograft/transplant host
- Toxicology
- Cell Biology Research
- Signal Transduction
- Immunology, Inflammation and Autoimmunity Research
- Autoimmunity
- lupus erythematosus
- lupus erythematosus, control
- Immunodeficiency Associated with Other Defects
- Immunodeficiency
- T cell deficiency
- specific T cell deficiency
- Intracellular Signaling Molecules
- T Cell Receptor Signaling Defects
- Autoimmunity
- Research Tools
- Cancer Research
- xenograft/transplant host
- Genetics Research
- Tissue/Cell Markers
- Tissue/Cell Markers: transplantation marker for embryonic and adult tissue
- Immunology, Inflammation and Autoimmunity Research
- T Cell Receptor Deficiency
- T cell deficiency
- T cell deficiency, xenograft/transplant host
- Toxicology Research
- xenograft/transplant host
- Cancer Research
Genotype: Tcratm1Mjo related
- Hematological Research
- Immunological Defects
- Immunology, Inflammation and Autoimmunity Research
- CD Antigens, Antigen Receptors, and Histocompatibility Markers
- Immunodeficiency
- Inflammation
- T Cell Receptor Signaling Defects
- Research Tools
- Cancer Research
- specific T cell deficiency
- Cancer Research
Mammalian Phenotype Terms by Genotype
The following phenotype information is associated with a similar, but not exact match to this JAX® Mice strain
Genotype: Tcratm1Mjo/Tcra+
NOD.129P2-Tcratm1Mjo
immune system phenotype
- abnormal T cell physiology
- unlike in wild-type controls no dual TCRA expressing cells are present (MGI Ref ID J:108590)
- decreased susceptibility to autoimmune diabetes
hematopoietic system phenotype
- abnormal T cell physiology
- unlike in wild-type controls no dual TCRA expressing cells are present (MGI Ref ID J:108590)
Genotype: Tcratm1Mjo/Tcra+
SJL.129P2-Tcratm1Mjo
immune system phenotype
- immune system phenotype
- no difference in the susceptibility to experimental autoimmune encephalomyelitis is detected compared to wild-type controls (MGI Ref ID J:108590)
Genotype: Tcratm1Mjo/Tcratm1Mjo
involves: 129P2/OlaHsd * BALB/c
immune system phenotype
- abnormal T cell morphology
- alphabeta+ T cells are completely absent (MGI Ref ID J:1292)
- abnormal immune system organ morphology
- (MGI Ref ID J:1292)
- abnormal splenic cell ratio
- elimination of alphabeta+ T cells is compensated for by an increase in splenic immunoglobulin positive cells (B cells) positive for IgM and IgD (MGI Ref ID J:1292)
- abnormal thymus cortex morphology
- the cortices of thymi in nulls are greatly expanded and tightly packed with CD4+CD8+ cells (MGI Ref ID J:1292)
- absent thymus medulla
- no medullae are discernible in mutant thymi (MGI Ref ID J:1292)
- enlarged thymus cortex
- (MGI Ref ID J:1292)
- increased B cell number
- in spleens compared to heterozygous controls (MGI Ref ID J:111129)
- increased IgE level
- in some mice compared to heterozygous controls (MGI Ref ID J:111129)
- increased IgG1 level
- in some mice compared to heterozygous controls (MGI Ref ID J:111129)
- increased activated T cell number
- on average 27% of the gamma-delta T cells are activated (MGI Ref ID J:111129)
- increased anti-double stranded DNA antibody level
- (MGI Ref ID J:111129)
- increased anti-nuclear antigen antibody level
- more than 80% of sera are positive for anti-nuclear antigens although the degree of reactivity varies (MGI Ref ID J:111129)
- increased autoantibody level
- about 50% of sera are reactive for mammalian cell proteins compared to only about 11% of sera from heterozygous controls (MGI Ref ID J:111129)
- by 5 weeks of age about 50% of mice show IgG autoantibodies in more than one assay (anti-dsDNA, anti-nuclear antigens, and immunoblotting for antibodies to mammalian cell proteins) (MGI Ref ID J:111129)
- reactivity in some mice is primarily against small nuclear ribonucleoproteins (MGI Ref ID J:111129)
- increased immunoglobulin level
- (MGI Ref ID J:111129)
- small Peyer's patches
- in mutants, these are smaller and shriveled in appearance compared to wild-type, being approximately half the size of controls (MGI Ref ID J:1292)
hematopoietic system phenotype
- abnormal T cell morphology
- alphabeta+ T cells are completely absent (MGI Ref ID J:1292)
- abnormal splenic cell ratio
- elimination of alphabeta+ T cells is compensated for by an increase in splenic immunoglobulin positive cells (B cells) positive for IgM and IgD (MGI Ref ID J:1292)
- abnormal thymus cortex morphology
- the cortices of thymi in nulls are greatly expanded and tightly packed with CD4+CD8+ cells (MGI Ref ID J:1292)
- absent thymus medulla
- no medullae are discernible in mutant thymi (MGI Ref ID J:1292)
- enlarged thymus cortex
- (MGI Ref ID J:1292)
- increased B cell number
- in spleens compared to heterozygous controls (MGI Ref ID J:111129)
- increased IgE level
- in some mice compared to heterozygous controls (MGI Ref ID J:111129)
- increased IgG1 level
- in some mice compared to heterozygous controls (MGI Ref ID J:111129)
- increased activated T cell number
- on average 27% of the gamma-delta T cells are activated (MGI Ref ID J:111129)
- increased immunoglobulin level
- (MGI Ref ID J:111129)
endocrine/exocrine gland phenotype
- abnormal thymus cortex morphology
- the cortices of thymi in nulls are greatly expanded and tightly packed with CD4+CD8+ cells (MGI Ref ID J:1292)
- absent thymus medulla
- no medullae are discernible in mutant thymi (MGI Ref ID J:1292)
- enlarged thymus cortex
- (MGI Ref ID J:1292)
Genotype: Tcratm1Mjo/Tcratm1Mjo
involves: 129P2/OlaHsd * MRL
renal/urinary system phenotype
- abnormal kidney morphology
- develop glomerular, interstitial and sometimes perivascular lesions (MGI Ref ID J:45448)
- increased urine protein level
- compared to age-matched B10.A mice (MGI Ref ID J:45448)
homeostasis/metabolism phenotype
- increased urine protein level
- compared to age-matched B10.A mice (MGI Ref ID J:45448)
Genotype: Tcratm1Mjo/Tcratm1Mjo
involves: 129P2/OlaHsd
immune system phenotype
- colitis
- decreased T cell proliferation
- proliferation in response to stimulation with the mitogen Con A is reduced compared to heterozygous controls (MGI Ref ID J:110898)
- enlarged mesenteric lymph nodes
- in mice removed from specific pathogen free conditions and exposed to environmental antigens compared to heterozygous controls (MGI Ref ID J:110898)
- enlarged spleen
- in mice removed from specific pathogen free conditions and exposed to environmental antigens compared to heterozygous controls (MGI Ref ID J:110898)
- increased T cell number
- increase in the abundance of TCRB+ TCRA- cells in mice exposed to environmental antigens (MGI Ref ID J:110898)
- increased activated T cell number
- a substantial proportion of the gamma-delta T cells in lymph organs of mice exposed to environmental antigens are activated (MGI Ref ID J:110898)
- increased gamma-delta T cell number
- a substantial proportion of the gamma-delta T cells are activated (MGI Ref ID J:110898)
- increase in gamma-delta T cells in the spleen, mesenteric lymph nodes, Peyer's patch lymph nodes and peripheral lymph nodes in mice exposed to environmental antigens compared to heterozygous controls (MGI Ref ID J:110898)
- spleen hyperplasia
- increase mean cell yield in mice removed from specific pathogen free conditions and exposed to environmental antigens compared to heterozygous controls (MGI Ref ID J:110898)
digestive/alimentary phenotype
- abnormal colon morphology
- in specific pathogen free mice areas of the colonic mucosa show hyperplasia, an increase in crypt fusion and crowding of the glands (MGI Ref ID J:37699)
- abnormal intestinal mucosa morphology
- colitis
- diarrhea
- occasionally seen in specific pathogen free mice (MGI Ref ID J:37699)
- rectal prolapse
- occasionally seen in specific pathogen free mice (MGI Ref ID J:37699)
nervous system phenotype
- abnormal neuron proliferation
- decrease in hippocampal neurogenesis (MGI Ref ID J:170591)
hematopoietic system phenotype
- decreased T cell proliferation
- proliferation in response to stimulation with the mitogen Con A is reduced compared to heterozygous controls (MGI Ref ID J:110898)
- enlarged spleen
- in mice removed from specific pathogen free conditions and exposed to environmental antigens compared to heterozygous controls (MGI Ref ID J:110898)
- increased T cell number
- increase in the abundance of TCRB+ TCRA- cells in mice exposed to environmental antigens (MGI Ref ID J:110898)
- increased activated T cell number
- a substantial proportion of the gamma-delta T cells in lymph organs of mice exposed to environmental antigens are activated (MGI Ref ID J:110898)
- increased gamma-delta T cell number
- a substantial proportion of the gamma-delta T cells are activated (MGI Ref ID J:110898)
- increase in gamma-delta T cells in the spleen, mesenteric lymph nodes, Peyer's patch lymph nodes and peripheral lymph nodes in mice exposed to environmental antigens compared to heterozygous controls (MGI Ref ID J:110898)
- spleen hyperplasia
- increase mean cell yield in mice removed from specific pathogen free conditions and exposed to environmental antigens compared to heterozygous controls (MGI Ref ID J:110898)
cellular phenotype
- abnormal neuron proliferation
- decrease in hippocampal neurogenesis (MGI Ref ID J:170591)
References
- Lawson BR; Koundouris SI; Barnhouse M; Dummer W; Baccala R; Kono DH; Theofilopoulos AN. 2001. The role of alpha beta+ T cells and homeostatic T cell proliferation in Y-chromosome-associated murine lupus. J Immunol 167(4):2354-60. PubMed: 11490025MGI: J:120153
Additional - Tcratm1Mjo related
- Au-Yeung BB; Katzman SD; Fowell DJ. 2006. Cutting edge: Itk-dependent signals required for CD4+ T cells to exert, but not gain, Th2 effector function. J Immunol 176(7):3895-9. PubMed: 16547221MGI: J:129883
- Binstadt BA; Hebert JL; Ortiz-Lopez A; Bronson R; Benoist C; Mathis D. 2009. The same systemic autoimmune disease provokes arthritis and endocarditis via distinct mechanisms. Proc Natl Acad Sci U S A 106(39):16758-63. PubMed: 19805369MGI: J:153217
- Blyth K; Vaillant F; Hanlon L; Mackay N; Bell M; Jenkins A; Neil JC; Cameron ER. 2006. Runx2 and MYC collaborate in lymphoma development by suppressing apoptotic and growth arrest pathways in vivo. Cancer Res 66(4):2195-201. PubMed: 16489021MGI: J:106649
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- Bour-Jordan H; Salomon BL; Thompson HL; Santos R; Abbas AK; Bluestone JA. 2007. Constitutive expression of B7-1 on B cells uncovers autoimmunity toward the B cell compartment in the nonobese diabetic mouse. J Immunol 179(2):1004-12. PubMed: 17617592MGI: J:131077
- Capone M; Cantarella D; Schumann J; Naidenko OV; Garavaglia C; Beermann F; Kronenberg M; Dellabona P; MacDonald HR; Casorati G. 2003. Human invariant V alpha 24-J alpha Q TCR supports the development of CD1d-dependent NK1.1+ and NK1.1- T cells in transgenic mice. J Immunol 170(5):2390-8. PubMed: 12594262MGI: J:82014
- Cobaleda C; Jochum W; Busslinger M. 2007. Conversion of mature B cells into T cells by dedifferentiation to uncommitted progenitors. Nature 449(7161):473-7. PubMed: 17851532MGI: J:126362
- Coles MC; Veiga-Fernandes H; Foster KE; Norton T; Pagakis SN; Seddon B; Kioussis D. 2006. Role of T and NK cells and IL7/IL7r interactions during neonatal maturation of lymph nodes. Proc Natl Acad Sci U S A 103(36):13457-62. PubMed: 16938836MGI: J:112903
- Correia-Neves M; Mathis D; Benoist C. 2001. A molecular chart of thymocyte positive selection. Eur J Immunol 31(9):2583-92. PubMed: 11536156MGI: J:115618
- Correia-Neves M; Waltzinger C; Mathis D; Benoist C. 2001. The shaping of the T cell repertoire. Immunity 14(1):21-32. PubMed: 11163227MGI: J:132246
- Corthay A; Nandakumar KS; Holmdahl R. 2001. Evaluation of the Percentage of Peripheral T Cells with Two Different T Cell Receptor alpha-Chains and of their Potential Role in Autoimmunity. J Autoimmun 16(4):423-9. PubMed: 11437490MGI: J:70152
- Crompton T; Gilmour KC; Owen MJ. 1996. The MAP kinase pathway controls differentiation from double-negative to double-positive thymocyte. Cell 86(2):243-51. PubMed: 8706129MGI: J:34462
- Di Santo JP; Aifantis I; Rosmaraki E; Garcia C; Feinberg J; Fehling HJ; Fischer A; von Boehmer H; Rocha B. 1999. The common cytokine receptor gamma chain and the pre-T cell receptor provide independent but critically overlapping signals in early alpha/beta T cell development. J Exp Med 189(3):563-74. PubMed: 9927518MGI: J:52569
- Dianda L; Hanby AM; Wright NA; Sebesteny A; Hayday AC; Owen MJ. 1997. T cell receptor-alpha beta-deficient mice fail to develop colitis in the absence of a microbial environment. Am J Pathol 150(1):91-7. PubMed: 9006326MGI: J:37699
- Elliott JI. 1998. Selection of dual Valpha T cells. Eur J Immunol 28(7):2115-23. PubMed: 9692880MGI: J:49315
- Elliott JI; Altmann DM. 1995. Dual T cell receptor alpha chain T cells in autoimmunity. J Exp Med 182(4):953-9. PubMed: 7561698MGI: J:108590
- Elliott JI; Altmann DM. 1996. Non-obese diabetic mice hemizygous at the T cell receptor alpha locus are susceptible to diabetes and sialitis. Eur J Immunol 26(4):953-956. PubMed: 8625995MGI: J:32586
- Faulkner L; Cooper A; Fantino C; Altmann DM; Sriskandan S. 2005. The mechanism of superantigen-mediated toxic shock: not a simple Th1 cytokine storm. J Immunol 175(10):6870-7. PubMed: 16272345MGI: J:119695
- Feuerer M; Herrero L; Cipolletta D; Naaz A; Wong J; Nayer A; Lee J; Goldfine AB; Benoist C; Shoelson S; Mathis D. 2009. Lean, but not obese, fat is enriched for a unique population of regulatory T cells that affect metabolic parameters. Nat Med 15(8):930-9. PubMed: 19633656MGI: J:152186
- Fowell DJ; Shinkai K; Liao XC; Beebe AM; Coffman RL; Littman DR; Locksley RM. 1999. Impaired NFATc translocation and failure of Th2 development in Itk-deficient CD4+ T cells. Immunity 11(4):399-409. PubMed: 10549622MGI: J:109489
- Furmanski AL; Saldana JI; Rowbotham NJ; Ross SE; Crompton T. 2012. Role of Hedgehog signalling at the transition from double-positive to single-positive thymocyte. Eur J Immunol 42(2):489-99. PubMed: 22101858MGI: J:179819
- Granucci F; Di Tota FP; Raimondi G; Citterio S; Rescigno M; Ricciardi-Castagnoli P. 2001. Autoreactive isotype-specific T cells determine B cell frequency. Eur J Immunol 31(1):215-24. PubMed: 11265637MGI: J:118406
- Hadeiba H; Locksley RM. 2003. Lung CD25 CD4 regulatory T cells suppress type 2 immune responses but not bronchial hyperreactivity. J Immunol 170(11):5502-10. PubMed: 12759427MGI: J:109990
- He Q; Morillon YM 2nd; Spidale NA; Kroger CJ; Liu B; Sartor RB; Wang B; Tisch R. 2013. Thymic development of autoreactive T cells in NOD mice is regulated in an age-dependent manner. J Immunol 191(12):5858-66. PubMed: 24198282MGI: J:207147
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- Hirota K; Turner JE; Villa M; Duarte JH; Demengeot J; Steinmetz OM; Stockinger B. 2013. Plasticity of TH17 cells in Peyer's patches is responsible for the induction of T cell-dependent IgA responses. Nat Immunol 14(4):372-9. PubMed: 23475182MGI: J:194909
- Hoglund P; Mintern J; Waltzinger C; Heath W; Benoist C; Mathis D. 1999. Initiation of autoimmune diabetes by developmentally regulated presentation of islet cell antigens in the pancreatic lymph nodes. J Exp Med 189(2):331-9. PubMed: 9892615MGI: J:52940
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- Karnowski A; Chevrier S; Belz GT; Mount A; Emslie D; D'Costa K; Tarlinton DM; Kallies A; Corcoran LM. 2012. B and T cells collaborate in antiviral responses via IL-6, IL-21, and transcriptional activator and coactivator, Oct2 and OBF-1. J Exp Med 209(11):2049-64. PubMed: 23045607MGI: J:190912
- Katayama M; Ohmura K; Yukawa N; Terao C; Hashimoto M; Yoshifuji H; Kawabata D; Fujii T; Iwakura Y; Mimori T. 2013. Neutrophils are essential as a source of IL-17 in the effector phase of arthritis. PLoS One 8(5):e62231. PubMed: 23671588MGI: J:200527
- Kern J; Drutel R; Leanhart S; Bogacz M; Pacholczyk R. 2014. Reduction of T cell receptor diversity in NOD mice prevents development of type 1 diabetes but not Sjogren's syndrome. PLoS One 9(11):e112467. PubMed: 25379761MGI: J:225316
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- LaBranche TP; Hickman-Brecks CL; Meyer DM; Storer CE; Jesson MI; Shevlin KM; Happa FA; Barve RA; Weiss DJ; Minnerly JC; Racz JL; Allen PM. 2010. Characterization of the KRN cell transfer model of rheumatoid arthritis (KRN-CTM), a chronic yet synchronized version of the K/BxN mouse. Am J Pathol 177(3):1388-96. PubMed: 20696780MGI: J:163689
- Labrecque N; Whitfield LS; Obst R; Waltzinger C; Benoist C; Mathis D. 2001. How much TCR does a T cell need? Immunity 15(1):71-82. PubMed: 11485739MGI: J:70595
- Le Campion A; Gagnerault MC; Auffray C; Becourt C; Poitrasson-Riviere M; Lallemand E; Bienvenu B; Martin B; Lepault F; Lucas B. 2009. Lymphopenia-induced spontaneous T-cell proliferation as a cofactor for autoimmune disease development. Blood 114(9):1784-93. PubMed: 19561321MGI: J:152255
- Luhder F; Chambers C; Allison JP; Benoist C; Mathis D. 2000. Pinpointing when T cell costimulatory receptor CTLA-4 must be engaged to dampen diabetogenic T cells. Proc Natl Acad Sci U S A 97(22):12204-9. PubMed: 11035773MGI: J:109887
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- Peng SL; Madaio MP; Hughes DP; Crispe IN; Owen MJ; Wen L; Hayday AC; Craft J. 1996. Murine lupus in the absence of alpha beta T cells. J Immunol 156(10):4041-9. PubMed: 8621947MGI: J:32944
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- Perona-Wright G; Mohrs K; Mayer KD; Mohrs M. 2010. Differential regulation of IL-4Ralpha expression by antigen versus cytokine stimulation characterizes Th2 progression in vivo. J Immunol 184(2):615-23. PubMed: 20018622MGI: J:159399
- Philpott KL; Viney JL; Kay G; Rastan S; Gardiner EM; Chae S; Hayday AC; Owen MJ. 1992. Lymphoid development in mice congenitally lacking T cell receptor alpha beta-expressing cells. Science 256(5062):1448-52. PubMed: 1604321MGI: J:1292
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